Lack of support for a role of the insulin gene variable number of tandem repeats minisatellite (INS-VNTR) locus in fetal growth or type 2 diabetes-related intermediate traits in United Kingdom populations

J Clin Endocrinol Metab. 2004 Jan;89(1):310-7. doi: 10.1210/jc.2003-030605.

Abstract

The insulin gene variable number of tandem repeats minisatellite (INS-VNTR) class III allele is associated with altered fetal growth, type 2 diabetes risk (especially when paternally inherited), and insulin and IGF2 gene expression. Further studies are needed to establish the role of the INS-VNTR in fetal growth and assess whether its effects depend on the parent of origin. We analyzed the INS-VNTR-linked -23 Hph1 polymorphism in 2283 subjects, comprising 1184 children and 1099 parents. There were no differences (P < 0.05) in birth weight between offspring of the three genotypes: III/III (n = 108) vs. I/I (n = 558), effect size, -8 g (P = 0.87); and I/III (n = 464) vs. I/I, effect size, -19 g (P = 0.54). We observed no differences in head circumference [III/III (n = 95) vs. I/I (n = 470), effect size, -0.14 cm; P = 0.31] or birth length. No differences were observed when stratifying by postnatal growth realignments [nonchangers III/III (n = 37) vs. I/I (n = 170), effect size, -43 g; P = 1.00] or by parent of origin of the class III allele (presence of paternal III allele effect size, -15 g; P = 0.74). INS-VNTR was nominally associated (P < 0.05) with body mass index and insulin resistance, but not with beta-cell function, in young adults. In the largest study to date, we found a lack of support for a role for INS-VNTR in fetal growth and nominal association with type 2 diabetes-related intermediate traits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Birth Weight / genetics
  • Body Height
  • Body Mass Index
  • Cephalometry
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • Embryonic and Fetal Development / genetics*
  • Fathers
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Growth / genetics
  • Humans
  • Insulin / genetics*
  • Insulin Resistance / genetics
  • Insulin-Like Growth Factor II / genetics
  • Minisatellite Repeats / genetics*
  • Polymorphism, Genetic
  • Pregnancy
  • United Kingdom

Substances

  • Insulin
  • Insulin-Like Growth Factor II